1. Field of the Invention
This invention relates to novel sweeteners. In particular, the invention relates to metal complexes of the N-alkylated aspartame derivative, N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester, i.e., neotame. The invention also relates to a liquid low calorie sweetener containing such metal complexes.
2. Related Background Art
It is known that various N-substituted derivatives of aspartame, such as disclosed in U.S. Pat. No. 5,480,668, are useful as sweetening agents. In particular, the N-alkylated aspartame derivative, N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester, is known as an extremely potent sweetening agent since its sweetening potency, on a weight basis, has been reported to be at least 50 times that of aspartame and about 10,000 times that of sucrose.
Since sweetening agents are often employed in aqueous solutions and beverages, it is important that they have an acceptable dissolution rate and an effective level of solubility to be commercially practicable. U.S. Pat. No. 4,031,258 describes certain inorganic salts of dipeptide sweeteners that provide improved dissolution and solubility. U.S. Pat. No. 4,448,716 describes dipeptide sweetener-metal complexes with improved dissolution rates, solubility and stability. N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester, however, is not disclosed or suggested.
It is known that the physical properties, as well as the stability of aspartame and other peptides can be modified by conversion to their salts. This is disclosed, for example, in U.S. Pat. Nos. 4,031,258 and 4,153,737. U.S. Pat. No. 4,153,737 also describes concentrated liquid low calorie sweeteners.
Structurally, however, N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester and aspartame differ in that, in N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester, a bulky neohexyl substituent is present on the amine nitrogen. ##STR2##
This structural difference results in dramatic differences in the physical and chemical properties of these compounds. For example, the melting point of N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester is 80.degree. C., while that of aspartame is 248.degree. C. In addition, N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester has much higher solubility in organic solvents than aspartame, and a much lower solubility in water. It is also known that N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester has a higher stability than aspartame under some pH conditions, as described in U.S. Pat. No. 5,480,688. The pronounced difference in sweetness between the two compounds is further evidence of their chemical dissimilarity.
Moreover, it is also known that a primary amino group such as the one on aspartame (pKa 7.7) generally has a different pKa than a secondary amino group such as the one on N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester (pKa 8.1). Moreover, the pKa's of an amino acid are known to have a profound impact on food applications (Labuza, T. P. and Basisier, M. W., 1992, "Physical Chemistry of Foods", H. G. Schwartzber and R. W. Hartel (Eds.), Marcel Dekker, Inc., New York). It is also well known that a secondary amine can not form Schiff base type compounds with carbonyl compounds while a primary amine may. Furthermore, N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl] -L-phenylalanine 1-methyl ester exhibits physiologically different behavior than aspartame as exemplified by the dramatic difference in sweetness. These differences are clearly indicative that the characteristics and properties of one can not be said to suggest those of the other.
While N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester is a highly potent sweetener, it is sparingly soluble in water and can give rise to dusting problems. Therefore, there is a need for N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester derivatives that have good dissolution and solubility properties in aqueous systems, and avoid dusting problems often encountered with fine powders. It would also be advantageous if the stability of N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester could be improved.